The objectives of the present proposal are to (a) quantify the behavioral and electroencephalographic (EEG) effects and concurrent physiological disposition of phencyclidine, (b) to find suitable antagonists to the toxic effects and/or pharmacological disposition of phencyclidine and (c) to gain an understanding of the mechanisms of action of phencyclidine. Standard laboratory techniques will be used to determine the dose-lethality spectrum and the blood and tissue distribution of phencyclidine in rats, guinea pigs, and dogs using both oral and intraperitoneal routes of administration. Additionally, the dose-response effects of phencyclidine on EEG and open-field behavior of rodents will be determined, as well as the dose-toxicity spectrum of phencyclidine, where toxicity is defined as convulsions for guinea pigs and dogs, and inability to balance on a rotor rod for rats. Once a pharmacological profile of phencyclidine has been established, various drugs (i.e., phenobarbital, phenytoin, carbamazepine, diazepam, ethosuximide, cannabidiol, phyostigmine, quipazine, haloperidol, activated charcoal and ammonium chloride) will be tested as possible antagonists of phencyclidine toxicity and/or in vivo distribution, using the measurements described above. By determining which drugs are effective phencyclidine antagonists, it will be possible to formulate and test hypotheses concerning the mechanisms of action of phencyclidine. It is anticipated that data derived from this collaborative interdisciplinary investigation will help to define and characterize the pharmacological spectrum of action of phencyclidine, including its possible mechanisms of action, and to evaluate possible antagonists of phencyclidine toxicity.